Acute Rheumatic Fever

What is Acute Rheumatic Fever?

Acute rheumatic fever (ARF) is an illness caused by an abnormal immune response to a throat infection caused by group A streptococci bacteria. This fever affects approximately 470,000 people every year and is more prevalent in developing countries where there exists wider cases of poorly treated or untreated throat infections. Each year, over 275,000 global deaths are tied to rheumatic heart disease. Factors contributing to the spread of the throat infection include crowded living conditions, lack of clean sanitation, and limited access to healthcare services.

The way ARF works is it triggers an unusual immune response to the throat infection. This reaction causes the body to attack its own cells due to their resemblance to bacteria. This can occur 2 to 4 weeks after the initial infection and may lead to heart inflammation, inflamed heart valves, abnormal body movements (Sydenham chorea), under-skin nodules, rashes (erythema marginatum), and moving joint pain (polyarthritis). Given the variation in severity and distribution of these symptoms among individuals, diagnosing ARF can be tough. Quick identification and treatment of ARF, using the modified Jones criteria, are crucial to handle the acute infection and to prevent complications. A severe long-term outcome of ARF is rheumatic heart disease, which can cause serious health issues and possibly, death.

What Causes Acute Rheumatic Fever?

Acute rheumatic fever (ARF) is essentially an inflammation in the body that happens because of a prior strep throat infection. Strep throat infections can lead to a variety of health problems, ranging from mild skin infections like impetigo and pharyngitis to more serious conditions like toxic shock syndrome and necrotizing fasciitis. It’s notable that ARF is more likely to occur after a strep throat infection rather than a skin infection. However, for certain high-risk groups, such as Indigenous Australians, skin infections like impetigo might be a significant contributor to ARF.

Generally, treating a strep throat infection with the right antibiotics will prevent ARF. However, people who have a strep throat infection and either don’t get medical care or have a silent infection without symptoms can end up with ARF. Social and environmental factors can also increase the risk of ARF. For example, crowded living conditions can contribute to the spread of strep throat infections and the subsequent development of ARF.

Risk Factors and Frequency for Acute Rheumatic Fever

Acute rheumatic fever (ARF) and rheumatic heart disease (RHD) account for around 470,000 new cases and 233,000 deaths every year. Thankfully, since the 1900s the frequency and seriousness of these conditions have reduced, largely due to improved living conditions, better medical care, and medications like penicillin. However, people who’ve had ARF in the past have about a 50% chance of it recurring if they get another untreated strep throat infection.

ARF can affect anyone, but it’s most often seen in kids aged 5 to 15. While both boys and girls can get ARF, girls are a bit more likely to go on to develop RHD. Alarmingly, ARF affects people in developing countries and Indigenous populations more than others due to their living conditions, limited treatment access, and higher rates of strep throat infection.

• There are approximately 470,000 new cases and 233,000 deaths from ARF and RHD every year.
• The frequency and severity of these conditions have decreased since the 1900s.
• ARF recurrence rate in high-risk patients, following untreated strep throat infection, is roughly 50%.
• ARF is primarily found in children between the ages of 5 to 15.
• No notable gender difference in ARF rates, but females are more likely to develop RHD.
• Developing countries and Indigenous populations show higher ARF rates owing to environmental and socioeconomic factors.

In the US, the rate of new ARF cases every year is around 10 in every 100,000 people, while in India it’s closer to 51 per 100,000. In Australia’s Indigenous population, the rate is between 150 to 380 cases per 100,000 children aged 5 to 14 years. Moreover, boys are more likely to be hospitalized due to ARF, especially those aged 6 to 11 of Asian and Pacific Islander descent.

Rheumatic heart disease, a common complication of ARF, currently affects an estimated 39 million people worldwide. However, the rates of ARF in Africa are unknown, but it’s believed that almost half of all RHD cases in children under 15 occur there.

Signs and Symptoms of Acute Rheumatic Fever

Acute Rheumatic Fever (ARF) is typically diagnosed based on certain clinical signs and usually occurs 2 to 4 weeks after an untreated GAS (Group A Streptococcus) infection, often a throat infection. Some patients may have had recurring skin infections linked to GAS. Interestingly, up to one-third of patients with ARF may not remember having a throat infection.

Symptoms of GAS throat infection can include fever, throat pain, headaches, and chills. Young children may also experience abdominal pain, nausea, and vomiting. If someone had an illness with these symptoms, doctors may consider the possibility of a GAS throat infection. Symptoms of ARF can vary a lot – from subtle signs to more severe cardiac disease. Most patients with ARF show general symptoms like fevers, chills, and fatigue. Joint issues, affecting larger joints like the knee, ankle, or wrist, are typically among the first signs of ARF, occurring in 60% to 80% of patients.

The most dangerous aspect of ARF is carditis (inflammation of the heart). Common signs of carditis are rapid heartbeat or the presence of a new heart murmur. Carditis in ARF affects 50% to 80% of patients, usually presenting about 2 to 3 weeks in and affecting different layers of the heart. It can also cause inflammation of the heart valves, mostly affecting the left-sided high-pressure valves. The mitral valves, impacted in 50% to 60% of valvulitis cases, generally have leakage as the initial sign. The progressive damage can lead to narrowing of the mitral valve.

• Aortic valve damage, affecting 20% of patients and leading to leakage, can also progress to valve narrowing.
• The tricuspid valve, affected only in 10% of patients, usually leads to tricuspid leakage.

ARF can evolve into Rheumatic Heart Disease (RHD) over time or multiple ARF episodes, due to damage to the heart valves. Even during ARF, severe inflammation of the heart or heart valve damage can lead to heart disease or heart failure.

Less common symptoms of ARF include skin outcomes like firm, painless nodules over joints (more common with severe carditis) and a non-itchy, pink or pale ring-like rash on the body, mainly seen in older kids. Emotional and neurological issues can also occur as symptoms of ARF, along with uncontrolled “jerking” movements of the face, hands, or feet, typically worse on one side and not present during sleep.

Testing for Acute Rheumatic Fever

The Revised Jones Criteria is commonly used to detect acute rheumatic fever (ARF), a disease that often follows a group A streptococcus (GAS) infection. The recognition of ARF is primarily based on specific markers and symptoms of the disease. In populations considered low risk, where ARF is found in two or fewer out of 100,000 school-aged children, the application of these criteria is mandatory. If a patient has two major markers or a combination of one major and two minor markers, they can be diagnosed with ARF. For recurring episodes of ARF, two major or three minor criteria or a combination of both are required.

ARF can also be considered as a probable diagnosis in patients who display signs of heart inflammation or slow-developing heart issues months after a GAS infection. An evaluation using an echocardiogram, a type of ultrasound that gives images of the heart, is recommended in these cases. Patients lacking evidence of a preceding GAS infection but meeting the initial criteria are also possibly suffering from ARF. The same applies to patients who show one major and one minor marker coupled with signs of a preceding GAS infection.

There are several ways to detect a GAS infection, which is usually the first step of diagnosing ARF. Throat swabs are the most reliable method, but the results take time. Tests that can be performed at the point of care are becoming more popular in primary healthcare settings. Other types of testing, such as nucleic acid amplification tests (NAAT) and rapid antigen detection tests (RADT), offer quicker results. However, the sensitivity of these tests might be less than 90%, requiring additional testing if results are negative. If knowledge of the specific type of GAS or its resistance to antibiotics is needed, neither NAAT nor RADT methods would be suitable.

For patients who might have had a GAS infection in the past, doctors can carry out serology tests that measure specific GAS antibodies in the blood. These tests can determine if an infection occurred as they show the immune system’s response which typically peaks 2 to 3 weeks after an infection. Interpretation of these tests depends on the patient’s age.

If ARF is suspected, all patients should undergo a cardiac evaluation as heart problems like valvulopathy (disease of the heart valves) or heart failure, are common in ARF. This evaluation usually includes chest x-rays, electrocardiography (ECG), and echocardiography. Sometimes, patients may have subclinical carditis, a condition where damage to the heart occurs without causing noticeable symptoms. Echocardiography is particularly useful in identifying this condition, and its accessibility is crucial for the effective treatment of ARF.

Treatment Options for Acute Rheumatic Fever

The treatment for Acute Rheumatic Fever (ARF), a disease caused by a Group A Streptococcus (GAS) infection, typically involves multiple approaches. This treatment usually includes getting rid of the GAS infection, relief for symptoms, and steps to prevent the disease from coming back. Usually, the initial treatment takes place in a hospital.

An antibiotic, usually penicillin, is the first step to treat and eradicate GAS. Even if the patient’s throat test for GAS comes back negative, they will still receive a course of antibiotics if diagnosed with ARF. The amount of penicillin a patient receives depends on their weight.

For patients who are allergic to penicillin, with a history of severe allergic reactions, other antibiotics such as cephalosporins or macrolides can be used. Occasionally, clindamycin might be used, although it’s known to cause gastrointestinal issues more often.

Alongside antibiotic treatment, the patient will receive symptomatic treatment to address the symptoms of ARF. Arthritis, which is often the first sign of ARF, can be treated with aspirin or non-steroidal anti-inflammatory drugs (NSAIDS) like naproxen, or possibly ibuprofen. These are used until the symptoms subside and may sometimes be paired with a proton-pump inhibitor, a medication to reduce stomach acid.

Steroids can be used if the patient can’t take aspirin or NSAIDS. Carditis, an inflammation of the heart, is a serious complication of ARF. Treatment usually consists of getting rid of the GAS infection, and limiting systemic inflammation to reduce the risk of developing cardiac disease. If the patient develops heart failure or rheumatic heart disease (RHD), treatment options could be medication-based or surgical, depending on how severe the disease is.

There are also manifestations of ARF that usually resolve on their own, such as skin nodules and a skin condition called erythema marginatum. Also, a late stage finding of ARF called Sydenham chorea (SC) is generally self-limited and can be managed with rest and avoidance of overstimulation. For patients whose daily life is impacted by SC, medication options include carbamazepine, pimozide, haloperidol, and valproic acid.

Patients who have had ARF are at risk for the disease recurring and developing into a worse form of rheumatic heart disease, so they should receive a secondary prevention treatment against GAS infections. This usually involves a monthly injection of penicillin G benzathine. For patients who are allergic to penicillin, macrolides and sulfadiazines can be used alternatively. If there’s a recurrence of GAS in the throat, clindamycin can be used before resuming with penicillin prevention treatment.

How long the secondary prevention treatment goes for can depend on whether there’s evidence of carditis. If someone has had detectable heart disease caused by carditis, they should continue prevention treatment for 10 years from the last episode of ARF, or by the time they turn 40, whichever comes later. If there is no sign of carditis, prevention treatment should continue for five years or until they turn 21, choosing whichever occurs last.

What else can Acute Rheumatic Fever be?

Patients with ARF, or Acute Rheumatic Fever, can show up with a wide range of symptoms. This makes the list of possible diagnoses extensive, and it really depends on the individual’s specific symptoms. Here are some conditions that doctors might consider if someone comes in with ARF symptoms:

• If the person is experiencing inflammation in multiple joints (polyarthritis), possible causes could include:
  • Lyme disease
  • Immune reaction following a strep infection (Poststreptococcal reactive arthritis)
  • An infection within a joint (Septic arthritis)
  • Reactions to medications or serum sickness
  • Post-infectious reactive arthritis
• If the issue seems to be with the heart (carditis), possible diagnoses include:
  • Inflammation of the heart’s inner lining due to an infection (Endocarditis)
  • Inflammation of the heart muscle usually caused by a viral infection (Viral myocarditis)
• If the person is showing signs of Sydenham Chorea (disordered movements or muscle control), doctors might consider:
  • Childhood mental disorders linked to strep infections (PANDAS)
  • The movement disorder Tardive Dyskinesia
  • Tourette Syndrome
• If there are skin issues involved, possibilities include:
  • Urticaria (hives)
  • Scarlet fever
  • Kawasaki disease
  • Erythema multiforme (a type of rash)
  • Erythema migrans, a sign of Lyme disease
  • A rash caused by a viral infection (Viral exanthem)
• For general systemic illnesses, options could be:
  • Juvenile idiopathic arthritis
  • Kawasaki disease
  • Systemic lupus erythematosus, an autoimmune disease

What to expect with Acute Rheumatic Fever

Acute Rheumatic Fever (ARF) typically lasts about 3 months, with a tendency to return in approximately 65% of cases. The recurrence can escalate the risk of the disease progressing to Rheumatic Heart Disease (RHD) and heart failure. Certain factors may increase the chances of recurrence like poor adherence to preventative measures, less time between ARF episodes, being younger, and having heart inflammation.

Of all complications, the involvement of the heart is crucial in determining the ARF’s outcome. Patients with heart inflammation face the highest risk of advancing to RHD, the major cause of disease and death in ARF patients. While treatment and living conditions have improved over the past century, reducing ARF’s long-term risks in developed regions, RHD in its late stage is still prevalent in less resourceful areas. For severe cases, valve replacement or repair may be necessary.

In a study of Australian patients with heart disease during an ARF episode, it was found that 50% of those with severe RHD needed valve surgery within 2 years with a death rate of around 10%. For patients with minor heart inflammation, 64% had mild heart disease even after 10 years of developing ARF. Out of these, nearly 11.4% progressed to severe RHD, and half required surgery.

A recent review compared the outcomes of mitral valve repair versus replacement. It was found that patients who had repair surgery typically faced lower death risks in the short and long term, although additional procedures were often necessary. Repair surgery is often a better choice for older individuals unless the patient also has aortic valve disease, in which case replacement might be beneficial.

Sydenham chorea (SC), a neurological disorder, typically resolves within 12 to 15 weeks. Some patients might face persistent SC, although the reason behind this is not clear. Some medical experts suspect that damage to a part of the brain might be the cause. It’s also worth noting that people who have had SC may exhibit more psychiatric symptoms.

Possible Complications When Diagnosed with Acute Rheumatic Fever

Rheumatic heart disease (RHD) is a common complication that can happen 10 to 20 years after Acute Rheumatic Fever (ARF). RHD happens due to damage to the heart valves which could be caused by severe or repeated episodes of ARF. Globally, RHD is a leading reason behind heart valve issues. Problems associated with RHD include heart failure, high blood pressure in the lungs, irregular heartbeats, stroke due to a blood clot, and sudden death due to heart issues.

Another complication from ARF is Jaccuod arthropathy. It’s a chronic but non-aggressive condition that can cause changes in joints similar to those seen in Rheumatoid Arthritis. This can include thumb subluxation (thumb displacement), ulnar deviation (the hands bend towards the pinky finger), hallux valgus (the big toe deviating from the center), and deformities of the fingers. But unlike in rheumatoid arthritis, patients with Jaccoud arthropathy don’t have any bone destruction, and the affected joints are flexible enough to return to normal.

Rarely, Sydenham’s chorea (an unusual movement disorder associated with ARF) can lead to ongoing symptoms and has been associated with more psychiatric symptoms in some patients.

Preventing Acute Rheumatic Fever

Acute Rheumatic Fever (ARF) and the following onset of Rheumatic Heart Disease (RHD) are major reasons for illness and death, particularly in less developed countries. To prevent these conditions, strategies are needed to prevent GAS throat infections, to identify and treat such infections early, and to safeguard against recurring ARF. Patient education is key for lifelong successful management of ARF.

Patients need to understand the potential problems related to their ARF diagnosis and the significance of sticking to the prevention medication therapy. Caregivers should also be informed about the signs of a GAS throat infection and the early indications of acute rheumatic fever. People living or studying around those who have returned from ARF are mostly likely to be exposed to the GAS infection.